Fabry’s disease is an X-linked lysosomal storage disorder. α-Galactosidase deficiency leads to accumulation of globotriaosylceramide mainly in endothelial and smooth muscle cells. Cerebrovascular symptoms with predo...Fabry’s disease is an X-linked lysosomal storage disorder. α-Galactosidase deficiency leads to accumulation of globotriaosylceramide mainly in endothelial and smooth muscle cells. Cerebrovascular symptoms with predominant affection of the vertebrobasilar circulation are one of the major sources of morbidity in Fabry’s disease. We present a Hungarian family with Fabry’s disease caused by a new mutation in the α-galactosidase A gene (GLA), and describe a variant expression of the disease. Megadolichoba- silar anomaly was diagnosed in two male patients in the family who died of thrombosis. In another female patient who had suffered from disturbance of the vertebrobasilar circulation, a strongly dilated basilar artery without thrombosis was found at autopsy. Another three family members had basilar strokes and large and elongated basilar arteries on MRI. Genetic analysis disclosed a c.47T→C missense mutation resulting in L16P in the amino acid sequence of the α-galactosidase protein. This report suggests that megadolichobasilar anomaly is potentially life-threaten- ing, and that L16P is a disease-causing mutation in patients with Fabry’s disease. Early enzyme replacement therapy may prevent the development of these irreversible cerebrovascular complications.展开更多
文摘Fabry’s disease is an X-linked lysosomal storage disorder. α-Galactosidase deficiency leads to accumulation of globotriaosylceramide mainly in endothelial and smooth muscle cells. Cerebrovascular symptoms with predominant affection of the vertebrobasilar circulation are one of the major sources of morbidity in Fabry’s disease. We present a Hungarian family with Fabry’s disease caused by a new mutation in the α-galactosidase A gene (GLA), and describe a variant expression of the disease. Megadolichoba- silar anomaly was diagnosed in two male patients in the family who died of thrombosis. In another female patient who had suffered from disturbance of the vertebrobasilar circulation, a strongly dilated basilar artery without thrombosis was found at autopsy. Another three family members had basilar strokes and large and elongated basilar arteries on MRI. Genetic analysis disclosed a c.47T→C missense mutation resulting in L16P in the amino acid sequence of the α-galactosidase protein. This report suggests that megadolichobasilar anomaly is potentially life-threaten- ing, and that L16P is a disease-causing mutation in patients with Fabry’s disease. Early enzyme replacement therapy may prevent the development of these irreversible cerebrovascular complications.
